This invention relates to .gamma.-thiobutyrolactone derivatives having useful anticonvulsant activity and, more particularly, to .alpha.- and/or .gamma.-substituted .gamma.-thiobutyrolactones.
Convulsant seizures are manifested in various chronic central nervous system (CNS) disorders, particularly epilepsies. These seizures are generally correlated with abnormal and excessive EEG discharges. A variety of drugs have been used for treatment of these seizures. Many of the older drugs are structurally related to phenobarbital, for example, the hydantoins, the deoxybarbiturates, the oxazolidinediones and the succinimides. More recently developed anticonvulsant compounds include the benzodiazepines, iminostilbenes and valproic acid.
Recently, several analogs of .gamma.-butyrolactone were synthesized and tested for their behavioral and electrophysiologic actions. It was found that those analogs substituted in the alpha position or in both the alpha and gamma positions and devoid of beta substituents were anticonvulsant and were inhibitory in the brain. Klunk, Covey and Ferrendelli, Mol. Pharmacol. 22(2), 438-443 (1982). By way of comparison, those analogs having substitutions in the beta position or in both the alpha and beta position were found to be convulsive compounds that were excitatory in brain tissue, in vivo and in vitro. Ibid., pp. 431-437. Studies of the structure-activity relationships of these compounds led to the development of a hypothetical molecular model explaining the convulsant and anticonvulsant properties of alkyl-substituted .gamma.-butyrolactones.